Submissions for variant NM_152296.5(ATP1A3):c.2851G>A (p.Glu951Lys)

dbSNP: rs2145942372

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002010428	SCV002290346	likely pathogenic	Dystonia 12	2022-10-17	criteria provided, single submitter	clinical testing	Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATP1A3 protein function. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 951 of the ATP1A3 protein (p.Glu951Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with alternating hemiplegia of childhood (PMID: 25996915, 26410222, 26417536). ClinVar contains an entry for this variant (Variation ID: 1499117). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneReviews	RCV002010428	SCV002559235	not provided	Dystonia 12		no assertion provided	literature only